Researchers from South Africa’s Aurum Institute, a health research facility, are spearheading a study to test whether widespread preventative use of the anti-tuberculosis (TB) drug, isoniazid, could dramatically reduce TB rates on a community-wide scale.
In partnership with three government departments, three major gold mining companies and mining unions, researchers from Aurum, the London School of Hygiene and Tropical Medicine (LSHTM) and Johns Hopkins University in the United States are offering isoniazid preventative treatment (IPT) to nearly 70 000 gold miners in South Africa.
Isoniazid is one of the main ingredients in first-line anti-tuberculosis drugs. IPT usually consists of a daily dose of medication for six to nine months for those vulnerable to, but not currently infected with, TB to prevent infection.
The project, called Thibela TB, is based on a study done in the 1950s among native Alaskans. During the first half of the 20th century the northern US state faced epidemic proportions of TB, with 15% of the total population infected and 90% of all children testing tuberculin positive by the age of six.
The state’s native Inuit were most affected: TB deaths within that population were the highest recorded. In response researchers developed the first community-wide IPT, or CW-IPT, administering the drug to all Inuit who did not have active TB. The results were astounding.
In just five years TB was reduced by almost 70%, with the bacterium nearly eradicated just two decades later. In South Africa IPT is primarily used for people living with HIV. It can reduce TB rates in HIV-positive people by 25%.
TB is the leading cause of death in developing countries for those living with the virus. Gavin Churchyard of the Aurum Institute proposed expanding IPT access after witnessing high rates of occupational TB among South Africa’s gold miners, who are especially susceptible to infection because of the dual epidemics of silicosis, a lung condition that results from silicosis dust released during gold mining, and HIV. While the adult HIV prevalence in South Africa sits at 18%, 30% of miners have the virus.
The impact of the two syndromes together is ‘multiplicative”, according to Churchyard, resulting in astronomical rates of TB: 89% of the population have latent TB and each year the disease becomes active in more than 4% of those.
Recognising the need to do something ‘drastic and radical” to stem the epidemic, researchers considered possible interventions.
According to Alison Grant of the LSHTM, a lead researcher on the study, a mathematical model done in 2000 ‘used existing data from the mines to look at what type of intervention would make a difference and [replicating the Alaska study] was the only one that really showed rapid change”.
Rather than using IPT on an individual level as is currently done, ‘we want to show that within a setting with HIV and high TB transmission, we can get a population level reduction of TB risk”, says Churchyard. The study breaks miners into an intervention arm and a control arm.
The control arm continues with the mine standard of care TB model, which researchers consider to be of ‘exceptional international standard”, while the intervention arm additionally offers IPT to any miner who does not have active TB.
Miners take IPT for nine months, with follow- ups continuing for two years to monitor preventative effects. Expectations for the programme are high.
Modelling predicted that the preventative effects would last for 10 years. Churchyard says that recent data suggests the impact could be sustained for much longer. Researchers are hoping for a 60% reduction in the burden of TB within the study’s population.
The study is now in its fourth year and final results regarding efficacy are expected some time in 2012. Preliminary results show a positive response by miners to the programme, with an uptake and retention of 80% in the last few clusters.
The programme also demonstrates the low risk of drug-resistant tuberculosis as a result of IPT, a fear that has impeded scaling up the therapy. Still, the long-term impact is far from understood. There are significant differences between the Alaskan setting of the 1950s and the South African one today.
While the former focused on TB prevention within homes, the Aurum study is broadening the population to include mines in several parts of South Africa. The Aurum study must also contend with HIV, non-existent in the 1950s, and a highly mobile population.
Recent studies have suggested that for those living with HIV, the effects of IPT may last only six months. Even if TB rates among miners were reduced, they could be infected when visiting communities not involved in the intervention.
To have a large impact, treatment may need to continue for longer or be repeated every few years and mining communities, as well as miners themselves, could need to undertake similar programmes.
Researchers hope this study will pave the way for CW-IPT that would reach the general population. There has been a request from the miners to extend the programme to their families, says Churchyard.
‘They say ‘Thibela is good for us, but what about our families?’ We need to make a strong case that this works first and then we can look at expanding it. ‘It is our hope that it is spectacularly successful,” says Churchyard, ‘but at the end of the day it is a trial.”